The main goals of the present research are to develop new chemical approaches to the study of biological membranes, their detailed chemical organization, dynamics and structure-function relationships. One central problem is to understand the nature of specific interactions between phospholipids and membrane proteins and those between different phospholipids. New cross-linking approaches are being developed for these problems. Syntheses of a variety of fatty acids containing "built-in" photosensitive groups have been carried out. For in vivo studies, the synthetic fatty acid derivatives are being incorporated into fatty acid auxotrophs of E. coli into a Pseudomonas auxotroph (host for PM2 lipid shell virus) and into mammalian cells and their viruses, e.g., sindbis virus. Photolysis should yield information on the nearest neighbor interactions. In vitro studies of a variety of systems possessing membrane functions will be performed using defined membrane proteins and synthetic phospholipids prepared from the photosensitive fatty acids. In addition to information on protein-phospholipid interactions, insights into membrane biogenesis and topography should accrue from these studies. The systems being studied are: (1) bacteriorhodopsin, a biological proton pump; (2) Beta-hydroxybutyrate dehydrogenase-lecithin interactions; (3) reconstitution of the major red cell siagloglycoprotein, glycophorin; (4) the orientation and topology of the M-13 virus coat protein in E.coli membrane; (5) the mechanism of action of the ionophore, gramicidin A; (6) cytochrome b5-cytochrome b5 reductase-stearyl desaturase interactions; (7) Ca ions/Mg ions ATPase of the sarcoplasmic reticulum. In in vivo studies, the mechanism of the mitogenic action of lipid A (LPS) is being studied by using mouse spleem lymphocytes.